title: Antiproliferative activity on human prostate carcinoma cell lines of new peptidomimetics containing the spiroazepinoindolinone scaffold.
abstract: Peptidomimetics containing the spiroazepinoindolinone scaffold were designed and synthesized in order to ascertain their antiproliferative activity on the DU-145 human prostatic carcinoma cell line. Ethyl 2'-oxa-1,2,3,5,6,7-hexahydrospiro[4H-azepine-4,3'-3H-indole]-1'-carboxylate scaffold was functionalized at nitrogen azepino ring with Aib-(l/d)Trp-OH dipeptides. Combining the different stereochemistries of the scaffold and the tryptophan, diastereoisomeric peptidomimetics were prepared and tested. Their biological activity was evaluated by proliferation studies proving that the isomer containing S spiroazepino-indolinone scaffold and l tryptophan is the most active compound. Docking studies confirmed that the active peptidomimetic could bind the GHSR-1a receptor with docking scores comparable with those of well-known agonists even though with a somewhat different binding mode.
authors.affiliation: DISFARM, sezione di Chimica Generale e Organica A. Marchesini, Università degli Studi di Milano, via Venezian 21, Milano 20133, Italy. sara.pellegrino@unimi.it
authors.forename: Sara
authors.initials: S
authors.lastname: Pellegrino
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Ruscica
authors.forename: Paolo
authors.initials: P
authors.lastname: Magni
authors.forename: Giulio
authors.initials: G
authors.lastname: Vistoli
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Gelmi
mesh_terms: D001381:Azepines / Q000737:chemistry; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004151:Dipeptides / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D062105:Molecular Docking Simulation; D057786:Peptidomimetics; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D017434:Protein Structure, Tertiary; D054440:Receptors, Ghrelin / Q000737:chemistry / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001381:Azepines; D004151:Dipeptides; D007211:Indoles; D057786:Peptidomimetics; D054440:Receptors, Ghrelin; D013141:Spiro Compounds; C030374:indole; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Docking; Ghrelin; Peptidomimetics; Prostate cancer